This project is aimed at teaming about the pathogenesis of inflammatory eye diseases grouped under the term "uveitis." Our effort in FY1990 focused on studies in experimental animals and has yielded the following main achievements: 1. The active site of the immunodominant and highly uveitogenic determinant of bovine interphotoreceptor retinoid-binding protein (IRBP) was localized to a nonapeptide at sequence 1182-1190. Four of the amino acids of this peptide were identified to be pivotal to its immunological activities; residues 1182 and 1190 are essential for its binding to the antigen presenting cell while 1188 and 1189 interact with the T cell receptor. 2. Lymphocytes become highly uveitogenic by their activation in culture. Data collected this period show dissociation between the generation of uveitogenicity and the proliferation of activated lymphocytes. 3. Concanavalin A (Con A), which stimulates vigorous proliferation responses in spleen (Sp) and lymph node (LN) cell cultures, also generates uveitogenicity in Sp cells, but not in LN cells. This lack of Con A effect in LN cultures was found to result from a deficiency in an accessory cell population present in the Sp. 4. Lymphocytes sensitized to non-dominant IRBP peptides do not recognize whole IRBP in culture as they do in the eye when mediating uveitis in rats. However, these lymphocytes do recognize IRBP following its digestion by endopeptidases. This finding provides an explanation for the aforementioned discrepancy and suggests that the recognition of IRBP in the eye is facilitated by its cleavage by tissue enzymes. 5. Rats injected with the uveitogenic peptide 1177-1191 in aqueous solution were found to be resistant to EAU induction by this peptide when it was injected in its uveitogenic form, in adjuvant emulsion. Furthermore, the treated rats were also resistant to induction of EAU by whole IRBP.